Control of enzymatic velocity under near-equilibrium conditions

Algebraic derivations demonstrate that if a multireactant enzyme system is poised at equilibrium and the concentration of one of the reactants is then changed by a small fraction, the resulting net reaction velocity is hyperbolically related to the fractional perturbation rather than the initial or final absolute concentration of that reactant. For small fractional perturbations the velocity is almost identical regardless which reactant is perturbed. Similar results are obtained even if the reaction system is already displaced by up to 30% from equilibrium at the time of the perturbation. These conclusions are independent of the relationships between the reactant concentrations and the kinetic constants for the enzyme. Thus under any near-equilibrium condition each of the reactants for a multireactant enzyme system shares almost equally in control of the net reaction velocity.     

Amoeboflagellate Transformations and the Gibbs-Donnan Ratio*

SYNOPSIS. A number of protozoa may have amoeboid, flagellated, or intergrade forms. At the present time several mechanisms have been proposed for inducing the formation of each of the above forms, but a definite triggering mechanism has not been elucidated. However, some change in the environment precedes the transformation of the cell from one form to another. Jahn (1962) and Czarska (1964), respectively, correlated ciliary reversal and water expulsion vesicle activity with alterations in the ionic environment. In both cases the processes involved are correlated with changes in the Gibbs-Donnan (G-D) relationship rather than direct ratios or molarities. It seems reasonable to assume that additional environmentally induced phenomena may also be based on changes in the relationship. The assumption is here made that an amoeboid cell, possessing the necessary genetic and physiologic potentials, can respond to certain changes in its environment by enflagellation. The following hypothesis is being considered: a change in the environment that increases the relative concentration of associated divalent cations is perhaps one of the main triggers for amoeba-to-flagellate transformations. Thus, in accordance with the G-D theory, this transformation would be expected to occur when a given ionic environment is diluted. In addition, the transformation is discussed in relation to pH, population density, and other environmental parameters that alter the Gibbs-Donnan ratio.     

Phases in potassium transport and their regulation under near-equilibrium conditions in wheat seedlings

Potassium uptake and release in roots and translocation to the shoots were studied in 14-day-old winter wheat ( Tritictum aestivum L. cv. Martonvásári 8) of different K status. Transport processes were measured in the growth solutions for 5 h ensuring near-equilibrium conditions. The uptake showed three phases: (1) at low external K⁺ concentrations it increased with increasing concentrations and culminated at 0.1 m M : (2) between 0.1 and 1 m M it decreased, and (3) it increased again above 1 m M : The release of K⁺ showed a constant low level below 1 m M while paralleling the uptake above that. The uncoupler 2,4-dinitrophenol inhibited uptake phases (1) and (2), whereas it did not affect either phase (3) or K⁺ release. Translocation showed similar patterns. It is concluded that phases (1) and (2) depend on metabolic energy while phase (3) is mostly passive. It is emphasized that different types of regulation seem to operate in the transport mechanism: i.e. limitation by transport sites, control by negative feedback and by K⁺/K⁺ exchange, respectively.     

The heart as a system of coupled nonlinear oscillators

In various approximations the heart is considered as a system of coupled nonlinear oscillators which are characterized by their phase transition curve (PTC) only. The system exhibits many phenomena which are known from ECG recordings such as multi-level-Wenckebach periodicity, dissociation, induction or removal of a tachycardia by an extrasystole, pseudo-block and the gap phenomenon. All these can be discussed within the model on a quantitative level.     

Quantitative interrelationship between Gibbs-Donnan equilibrium, osmolality of body fluid compartments, and plasma water sodium concentration.

The presence of negatively charged, impermeant proteins in the plasma space alters the distribution of diffusible ions in the plasma and interstitial fluid (ISF) compartments to preserve electroneutrality. We have derived a new mathematical model to define the quantitative interrelationship between the Gibbs-Donnan equilibrium, the osmolality of body fluid compartments, and the plasma water Na+ concentration ([Na+]pw) and validated the model using empirical data from the literature. The new model can account for the alterations in all ionic concentrations (Na+ and non-Na+ ions) between the plasma and ISF due to Gibbs-Donnan equilibrium. In addition to the effect of Gibbs-Donnan equilibrium on Na+ distribution between plasma and ISF, our model predicts that the altered distribution of osmotically active non-Na+ ions will also have a modulating effect on the [Na+]pw by affecting the distribution of H2O between the plasma and ISF. The new physiological insights provided by this model can for the first time provide a basis for understanding quantitatively how changes in the plasma protein concentration modulate the [Na+]pw. Moreover, this model defines all known physiological factors that may modulate the [Na+]pw and is especially helpful in conceptually understanding the pathophysiological basis of the dysnatremias.     

The development of the early atrioventricular conduction system in the embryonic heart

Recent electrophysiological evidence indicates that periodic spontaneous depolarizations occur in the primordial heart of the bird (and presumably mammal) even before the myocardial cells can contract, and these are initiated in the primordial sinoatrial region. As contractions are generated, these then establish a peristaltic wave. From that time on, during ontogenesis, the contractile sequence follows a regular pattern of development. As chambers form they contract sequentially in the direction of blood flow, even though, in the twisted configuration, myocardial continuities suggest the possibility of short-circuiting the electrical conduction pathways from atrium to bulbus. This implies that, even at these early stages, the electrical properties of the myocardium are not isotropic, and that specialized conduction pathways must exist. To the present time, electrophysiological techniques have limited the direct evidence that can be obtained on these delicate electrically specialized pathways. However, microscopical techniques have permitted studies on the morphological development of the tissue and of the cells in the various regions of the myocardium. The present paper traces the development of cell morphology in these regions, including the development of structural nodes and proximal ventricular fibre pathways, and from these observations, the manner in which the electrical conduction pathways are believed to develop is suggested.     

The role of Jak/STAT signaling in heart tissue renin-angiotensin system

The involvement of the Renin Angiotensin System (RAS) and the role of its primary effector, angiotensin II (Ang II), in etiology of myocardial hypertrophy and ischemia is well documented. In several animal models, the RAS is activated in cardiac cell types that express the receptor AT₁, and/or AT₂, through which the Ang II mediated effects are promoted. In this article, we briefly review recent experimental evidence on the critical role of a prominent signaling pathway, the Jak/Stat pathway in activation and maintenance of the local RAS in cardiac hypertrophy and ischemia. Recent studies in our laboratory document that the promoter of the prohormone angiotensinogen (Ang) gene serves as the target site for STAT proteins, thereby linking the Jak/Stat pathway to activation of heart tissue autocrine Ang II loop. Stat5A and Stat6, are selectively activated when the heart is subjected to ischemic injury, whereas activation of Stat3 and Stat5A is involved in myocardial hypertrophy. Blockage of RAS activation by treatment with specific inhibitor promotes a remarkable recovery in functional hemodynamics of the myocardium. Thus, activation of selective sets of Stat proteins constitutes the primary signaling event in the pathogenesis of myocardial hypertrophy and ischemia.     

The fish heart as a model system for the study of myoglobin

A model is presented for myoglobin study based upon naturally occurring differences in myocardial myoglobin content in fish. The sea raven (Hemitripterus americanus) and the ocean pout (Macrozoarces americanus) have heart myoglobin contents of approx. 65 and 5 nmol/g wet wt, respectively. The maximal activities of enzymes associated with energy metabolism are similar in the two hearts. Isolated perfused hearts performed with similar efficiencies based upon similar rates of work, oxygen consumption and lactate production. Under normoxic perfusion conditions both hearts met 98% of the ATP demand by oxidative mechanisms. Myoglobin-rich sea raven hearts performed significantly better than myoglobin-poor ocean pout hearts under conditions of hypoxia and glycolytic blockage. The performance of sea raven hearts was impaired during hypoxia by decreasing the content of functional myoglobin with hydroxylamine. No effect upon performance was observed with the ocean pout heart. The data provide the first evidence that myoglobin plays a role in the maintenance of contractility in heart under hypoxic conditions.